阿那曲唑可有效预防高危女性乳腺癌
作者：
小柯机器人 发布时间：2019/12/16 17:49:45
英国伦敦玛丽女王大学Jack Cuzick研究小组在研究中取得进展。他们分析了使用阿那曲唑预防乳腺癌的长期效果。这一研究成果发表在2019年12月12日出版的国际学术期刊《柳叶刀》上。
两项大型临床试验表明，在使用芳香化酶抑制剂后的5年随访中，高危妇女乳腺癌的发生率有所降低。
IBIS-II是一项国际性、随机、双盲、安慰剂对照试验。2003年2月2日至2012年1月31日，研究组共招募了3864名绝经后乳腺癌风险增加的女性，按1：1随机分组，1920名女性接受阿那曲唑治疗，1944名接受安慰剂治疗，为期5年。
研究组每年都对这些女性进行随访。中位随访131个月后，阿那曲唑组的乳腺癌发病率下降49%，前5年下降幅度较大，但5年后仍有显著性差异，不过与前5年相比差异不显著。
浸润性雌激素受体阳性乳腺癌发病率降低54%，且在治疗结束后持续有效。导管原位癌的发病率降低了59%，尤其是雌激素受体阳性的患者。两组患者的总死亡率和乳腺癌死亡率均无显著差异。阿那曲唑亦可显著降低非乳腺癌的发病率，主要为非黑色素瘤性皮肤癌。两组均未发现骨折或心血管疾病发生率增加。
总之，阿那曲唑可显著降低乳腺癌高危患者的患癌率，且没有新的毒副作用。
附：英文原文
Title: Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial
Author: Jack Cuzick, Ivana Sestak, John F Forbes, Mitch Dowsett, Simon Cawthorn, Robert E Mansel, Sibylle Loibl, Bernardo Bonanni, D Gareth Evans, Anthony Howell
Issue&Volume: December 12, 2019
Abstract:
Background
Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period.
Methods
IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer.
Findings
3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105–156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39–0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27–0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45–0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33–0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22–0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78–0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69–1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57–0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed.
Interpretation
This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.
DOI: 10.1016/S0140-6736(19)32955-1
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext
